Ankylosing spondylitis (AS) is a chronic inflammatory disease possessing a morbid serum microenvironment with enhanced oxidative stress. Long-term exposure to an oxidative environment usually results in cellular senescence alone with cellular dysfunction. Mesenchymal stem cells (MSCs) are a kind of stem cell possessing strong capabilities for immunoregulation, and senescent MSCs may increase inflammation and participate in AS pathogenesis. The objective of this study was to explore whether and how the oxidative serum environment of AS induces MSC senescence. Here, we found that AS serum facilitated senescence of MSCs in vitro, and articular tissues from AS patients exhibited higher expression levels of the cell cycle arrest-related proteins p53, p21 and p16. Importantly, the levels of advanced oxidative protein products (AOPPs), markers of oxidative stress, were increased in AS serum and positively correlated with the extent of MSC senescence induced by AS serum. Furthermore, MSCs cultured with AS serum showed decreased mitochondrial membrane potential and ATP production together with a reduced oxygen consumption rate. Finally, we discovered that AS serum-induced mitochondrial dysfunction resulted in elevated reactive oxygen species (ROS) in MSCs, and ROS inhibition successfully rescued MSCs from senescence. In conclusion, our data demonstrated that the oxidative serum environment of AS facilitated MSC senescence through inducing mitochondrial dysfunction and excessive ROS production. These results may help elucidate the pathogenesis of AS and provide potential targets for AS treatment.
The pathogenesis of reactive arthritis (ReA) has not been fully elucidated. In recent years, many researchers have confirmed that multiple cytokines are involved in the occurrence and development of ReA. Although ReA is self-limiting, it is still incurable for some patients who have no or a weak response to traditional drugs, such as non-steroidal anti-inflammatory agents, glucocorticoids and immunosuppressive agents. This is called refractory reactive arthritis. Currently, there is insufficient evidences for the treatment of refractory ReA with biological agents, though biological agents against cytokines have been developed over the past few years. This review summarizes the current development of clinical treatments of ReA with biological agents, which provides future investigations on refractory ReA with more evidence and references.
Background:To explore long-non-coding RNA (lncRNAs),messenger RNAs (mRNAs) expression profiles and biological functions in the urine samples in lupus nephritis (LN) patients.Methods:Three LN patients and three healthy controls(con) were recruited,whose midstream morning urine was collected.A microarray of mRNA and lncRNA was applied to explore total RNA expression variation.Then venn analysis was applied to screen out specific gene expression in the LN group compared to the con group.Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to reveal the gene functions of the dysregulated lncRNA-associated with LN;STRING online website and Cytoscape software network analysis were applied to construct protein interaction network (PPI) and screen out the Hub Gene.Drug online websites were conducted as drug prediction websites.Results:A total of 273 mRNAs and 549 lncRNAs were differentially expressed in LN patients' urine compared with the con group.GO analysis of LN revealed that mRNAs from the lncRNA-mRNA network were enriched in terms of antigen-negative regulation of immune response.KEGG analysis of hub genes related to the LN lncRNA-mRNA network highlights their critical role in protein processing in the endoplasmic reticulum,P53 signaling pathway.Co-expression and PPI network analysis suggested that high-degree nodes are clustered in apoptosis,autophagy, reactive oxygen species pathway.Drug prediction indicated that the targeted drugs mainly included antioxidant activity,phosphorylative mechanism.Conclusion:Our findings indicated that the differential expressed urinary lncRNAs(DELs) possessed considerable clinical value in the diagnosis and potential therapeutic applications of drugs in LN patients.
In theory of topological classification, the 2D topological superconductors without time reversal symmetry are characterized by Chern numbers. However, in reality, we find the Chern numbers can not reveal the whole properties of the boundary states of the topological superconductors. We figure out some particle-hole symmetry related Z2 invariants, which provide more additional information of the topological superconductors than the Chern numbers provide. With the Z2 invariant, we define weak and strong topological superconductors in 2D systems. Moreover, we explain the causes of mismatch between the Chern numbers and the numbers of boundary states in topological superconductors, and claim that the robust Majorana zero modes are characterized by the Z2 invariant rather than the Chern numbers. We also extend the Z2 invariants to 3D non-time-reversal symmetry superconductor systems including gapful and gapless situations.
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